Plasma Fluorescence Scanning and Fecal Porphyrin Analysis for the Diagnosis of Variegate Porphyria: Precise Determination of Sensitivity and Specificity with Detection of Protoporphyrinogen Oxidase Mutations as a Reference Standard

Abstract

Background: Variegate porphyria (VP) is the autosomal dominant disorder associated with deficiency of the enzyme protoporphyrinogen oxidase (PPOX). Plasma fluorescence scanning has been reported to be a more sensitive test for VP than traditional fecal chromatography. Previous comparisons of these techniques predated identification of the PPOX gene. We assessed these techniques in a large group of patients characterized for VP at the DNA level. Methods: We evaluated all patients for whom the genotype and a plasma scan or fecal porphyrin result were available. Mutations were detected by restriction digest analysis. Plasma fluorescence scanning was conducted according to published methods. Fecal porphyrins were identified and quantified by thin-layer chromatography. Results: Plasma fluorescence scanning was assessed in 679 patients (205 with VP who were carriers of a PPOX mutation, either with disease symptoms or asymptomatic) and fecal analysis in 473 (190 with VP). Sensitivity and specificity of both tests were higher in adults than in children and higher for adults with disease symptoms than for asymptomatic carriers. In a direct comparison in 168 adults (73 with VP), plasma scanning was signifi-

Diagnosing Acute Porphyrias

“…Although as expected for VP (1, 10, 15 ) the median concentrations of protoporphyrin and coproporphyrin were increased in feces, with the former exceeding the latter, coproporphyrin was found to be the better predictor of VP (9 ). However, protoporphyrin, as measured by the authors (9 ), includes other dicarboxylic porphyrins that may predominate in normal feces.…”

“…In all of the acute porphyrias except VP and in porphyria cutanea tarda a fluorescence emission peak around 620 nm may be present (10,12 ). The test is simple but requires a fluorescence spectrometer with a red-sensitive photomultiplier (9 ).…”

Functional Characterization of Five Protoporphyrinogen oxidase Missense Mutations Found in Argentinean Variegate Porphyria Patients

“…Also, it is very important to identify latent carriers to provide adequate counseling to avoid precipitating factors that trigger acute attacks. Plasma fluorescence scanning is the most reliable and easy method to detect patients with VP (Enriquez de Salamanca et al 1993;Hift et al 2004). However, it may be negative in asymptomatic carriers and children (Hift et al 2004;Schneider-Yin and Minder 2006).…”

“…Plasma fluorescence scanning is the most reliable and easy method to detect patients with VP (Enriquez de Salamanca et al 1993;Hift et al 2004). However, it may be negative in asymptomatic carriers and children (Hift et al 2004;Schneider-Yin and Minder 2006). Therefore, when a disease-causing mutation has been identified in a proband, the screening of this mutation in asymptomatic relatives is recommended to detect latent carriers within a family (Hift et al 2004).…”

“…However, it may be negative in asymptomatic carriers and children (Hift et al 2004;Schneider-Yin and Minder 2006). Therefore, when a disease-causing mutation has been identified in a proband, the screening of this mutation in asymptomatic relatives is recommended to detect latent carriers within a family (Hift et al 2004). For mutations with no obvious negative consequences, it is important to prove their deleterious effect with expression assays and exclude neutral polymorphisms.…”